In modern medicine, the choice for therapeutic approaches often depends on the stage of the disease process. This principle holds true in the majority diseases like cancer, neurological and psychiatric disorders, many infections but also applies for cardiovascular and metabolic diseases such as heart failure, peripheral artery disease, diabetes, hypertension and angina pectoris. Stage-specific therapy has largely contributed to the strong increase in life expectancy in our society and more specifically to the reduction of mortality of cardiovascular diseases.
In atrial fibrillation (AF), a classification of the disease does not exist yet which is due to the fact that the main electrophysiological alterations which determine the stability of AF have only been identified very recently. Two electrophysiological techniques that are currently used for the quantification of the complexity of the substrate of AF include time frequency analysis of surface electrocardiograms (ECGs) and ECG imaging. The first technique uses Fast-Fourier or principle component analysis of the atrial surface ECG signal and can adequately estimate the complexity of AF in the right but not in the left atrium. Because the complexity of the AF substrate is larger in the posterior wall of the left atrium compared to the right atrial free wall and because the left atrium is more important for the stability of AF, this technique is not likely to provide an adequate classification of AF or a good estimation of the success of AF therapy. The second technique has been developed to reconstruct the epicardial electrical activity in atria and ventricles from body surface potential maps and the individual anatomy of the thorax. In order to implement this technique, an ECG-triggered CT or MRI of the thorax including localization of the electrodes is required, which are expensive, time-consuming and, in case of CT, afflicted with radiation exposure.
Consequently, current therapeutic regimens are most often chosen based on clinical symptoms and the duration of AF (paroxysmal or persistent AF). Although helpful, these categories do not necessarily reflect the quality and the degree of electrophysiological changes resulting in AF. For example, in patients with persistent AF the relative contribution of abnormal impulse formation or the severity of the electrophysiological substrate are usually unknown and not taken into account during the therapeutic decision-making process. Yet it appears likely that the nature of the electrophysiological changes resulting in AF strongly affects the efficacy of a therapeutic intervention emphasizing the need for a classification of AF.
The main advantage of the classification of AF would be the possibility to implement a “graded therapy” of AF. A “graded therapy” is a therapy that depends on the kind and the degree of the electrophysiological alterations in a specific patient. A large variety of therapeutic options exist in AF patients: pharmacological cardioversion, electrical cardioversion, pulmonary vein isolation, extended ablation therapies, rate control, anticoagulant therapy, and organ-protective upstream therapy. The challenge is to choose the right therapy for the right patient. In order to define the best choice in an individual patient, the kind and degree of pathophysiological changes in the atrium needs to be determined which means to classify the arrhythmia in each individual patient. Furthermore, such a classification will allow basic researchers and clinicians to better understand the mode of action of anti-arrhythmic drugs and to evaluate new anti-arrhythmic working mechanisms, to develop individualized therapy with anti-arrhythmic drugs, and to optimize ablation therapies in terms of patient selection, ablation technique (RF, ultrasound, cryo), and selection of ablation sites.
As the foregoing illustrates, there is a need to provide means for classifying AF in a manner that eliminates at least some of the drawbacks described above.